Metabolic Syndrome Fuels Genomic Instability? Insights from a Pilot Study on Colorectal Cancer

Background/Objectives: Metabolic syndrome (MS) impacts 25% of the adult population worldwide and elevates the risk of colorectal cancer by 40%. Microsatellite instability (MSI) resulting from impaired DNA mismatch repair serves as a critical biomarker for selecting patients for immunotherapy. Methods: This single-center pilot study examined the correlations between MS and MSI in 157 individuals with surgically treated colorectal cancer. Patients were categorized according to the International Diabetes Federation Metabolic Syndrome criteria. The MSI status was assessed using immunohistochemical investigation of mismatch repair proteins. The statistical analysis encompassed chi-square tests and the computation of odds ratios. Results: Patients with MS exhibited a substantially greater prevalence of MSI compared to controls (15.5% vs. 9.8%, p < 0.05) corresponding to a 1.63-fold increase in odds. The co-occurrence of MSI and hepatic steatosis displayed a strong association within the MS group (OR: 5.81), indicating a 2.6-fold increased prevalence relative to controls. Conclusions: This pilot investigation offers initial evidence associating MS with a heightened frequency of MSI in colorectal cancer. The strong association with hepatic steatosis indicates common metabolic-genomic pathways. The findings advocate for the incorporation of metabolic assessment into precision oncology for the selection of immunotherapy, necessitating multicenter validation studies.